OBJECTIVE: To examine the interaction between the GABA and glutamate neuronal systems. RESULTS We previously showed that infusion of an antisense oligo for GAD67 mRNA into the S-ME for 6 h stimulates LHRH release in prepubertal monkeys (J. Neurosci. 16:2563-2573, 1996). Since glutamate is the precursor for GABA synthesis with GADs, and since it stimulates LHRH release in the S-ME, it is possible that the LHRH increase with infusion of the antisense oligo for GAD mRNAs is due to an increase in glutamate, as well as a decrease in GABA. Therefore, in this study, we measured GABA and glutamate in the same perfusate samples measured for LHRH. As expected, GABA release significantly decreased during the first 1 h of antisense infusion. This decrease in GABA release continued for the remaining 6 h, and did not recover for an additional 6 h of the post-infusion period. In contrast, glutamate release tended to increase slightly at the 4th-6th h of infusion in some cases, but the overall mean did not significantly change during the entire 6 h of antisense infusion. Glutamate release, however, increased significantly in the first 3 h of the post-infusion period. These results indicate that an increase in LHRH release by infusion of the antisense oligo for GAD67 mRNA into the S-ME is primarily due to the decrease in GABA release, which is the result of the reduced GAD synthesis. However, the slight increase in glutamate release, as well as the relative increase in glutamate tone due to the decrease in GABA release, may contribute to the increase in LHRH release. This study further supports our hypothesis that the developmental reduction in GAD synthesis and GABA release is an important factor for the onset of puberty. FUTURE DIRECTIONS We will increase the number of cases in this study. KEY WORDS GABA, glutamate, GAD, antisense DNA HD11355 & RR00167